It sometimes happens that low dose acetylsalicylic acid administered to suppress thrombus and/or embolization (antiplatelet therapy) in cerebrovascular and circulatory diseases induces gastric ulcer or duodenal ulcer. Since discontinuation of administration of acetylsalicylic acid may result in thrombus and/or embolization, it is considered important to continue administration of low dose acetylsalicylic acid while suppressing the onset of ulcer.
While acetylsalicylic acid is also known as a non-steroidal anti-inflammatory drug (NSAIDs), and mainly used for the treatment of pain, fever and inflammation, non-steroidal anti-inflammatory drug may cause gastric ulcer or duodenal ulcer. Particularly, in the treatment of rheumatoid arthritis, osteoarthritis and the like, discontinuation of administration of non-steroidal anti-inflammatory drug may be difficult, since it markedly degrades the quality of life (QOL). Therefore, it is considered important to continue administration of non-steroidal anti-inflammatory drug while suppressing the onset of ulcer.
On the other hand, since PPIs of benzimidazole compounds (e.g., lansoprazole, omeprazole and the like) have a strong gastric acid secretion-inhibitory action, a gastric mucosa-protective action and the like, they have been widely used as therapeutic agents for peptic ulcer and the like. Particularly, lansoprazole preparation has obtained an approval also in Japan in recent years on the efficacy of “suppression of onset of gastric ulcer or duodenal ulcer by administration of low dose acetylsalicylic acid” and “suppression of onset of gastric ulcer or duodenal ulcer by administration of non-steroidal anti-inflammatory drug”, and a clinical effect of suppression of the onset of gastric ulcer or duodenal ulcer due to the dosing of acetylsalicylic acid has been demonstrated.
Patent document 1 (WO 97/25064) discloses an oral pharmaceutical dosage form for oral administration, which contains an acid susceptible proton pump inhibitor with at least one kind of non-steroidal anti-inflammatory drug and, when desired, a pharmaceutically acceptable diluent.
Patent document 2 (WO 2007/064274) discloses an oral pharmaceutical dosage form comprising, as active ingredients, an acid susceptible proton pump inhibitor together with acetyl salicylic acid or a derivative thereof and optionally pharmaceutically acceptable diluents, characterized in that the dosage form is in the form of an oral fixed combination dosage form comprising a group of separate physical units comprising the acid susceptible proton pump inhibitor and one or more other separate physical units comprising the acetyl salicylic acid or a derivative thereof, and wherein at least the proton pump inhibitor is protected by an enteric coating layer.
Patent document 3 (WO 2005/076987) discloses a pharmaceutical composition comprising: (a) a therapeutically effective amount of at least one acid labile proton pump inhibitor; (b) at least one buffering agent in an amount sufficient to increase gastric fluid pH to a pH that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid; and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug.
Patent document 4 (WO 2002/098352) discloses a pharmaceutical composition in unit dose form suitable for oral administration to a patient, comprising: (a) an acid inhibitor present in an amount effective to raise the gastric pH of said patient to at least 3.5 upon the administration of one or more of said unit dosage forms; (b) a non-steroidal anti-inflammatory drug in an amount effective to reduce or eliminate pain or inflammation in said patient upon administration of one or more of said unit dosage forms; and wherein said unit dosage form provides for the coordinated release of said acid inhibitor followed by said non-steroidal anti-inflammatory drug.
While PPI such as lansoprazole and the like and acetylsalicylic acid have already been commercially available as single agents, a dry coated tablet containing both PPI and acetylsalicylic acid is not known.